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芽孢杆菌 sigma 因子抑制剂 CsfB 的结构与功能研究进展

Structural and Functional Insights into Bacillus subtilis Sigma Factor Inhibitor, CsfB.

机构信息

Department of Chemistry, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, UK.

Department of Chemistry, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, UK; Structural Biology and Biophysics Unit, Fondazione Ri.MED, Via Bandiera, 11, 90133 Palermo, Italy.

出版信息

Structure. 2018 Apr 3;26(4):640-648.e5. doi: 10.1016/j.str.2018.02.007. Epub 2018 Mar 8.

DOI:10.1016/j.str.2018.02.007
PMID:29526435
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5890618/
Abstract

Global changes in bacterial gene expression can be orchestrated by the coordinated activation/deactivation of alternative sigma (σ) factor subunits of RNA polymerase. Sigma factors themselves are regulated in myriad ways, including via anti-sigma factors. Here, we have determined the solution structure of anti-sigma factor CsfB, responsible for inhibition of two alternative sigma factors, σ and σ, during spore formation by Bacillus subtilis. CsfB assembles into a symmetrical homodimer, with each monomer bound to a single Zn ion via a treble-clef zinc finger fold. Directed mutagenesis indicates that dimer formation is critical for CsfB-mediated inhibition of both σ and σ, and we have characterized these interactions in vitro. This work represents an advance in our understanding of how CsfB mediates inhibition of two alternative sigma factors to drive developmental gene expression in a bacterium.

摘要

全球范围内细菌基因表达的变化可以通过 RNA 聚合酶的替代σ(σ)因子亚基的协调激活/失活来调控。σ 因子本身通过反σ因子以多种方式进行调节。在这里,我们确定了负责抑制枯草芽孢杆菌孢子形成过程中两个替代σ因子σ和σ的抗σ因子 CsfB 的溶液结构。CsfB 组装成对称的同源二聚体,每个单体通过一个高音谱号锌指折叠结合到单个 Zn 离子上。定点突变表明二聚体形成对于 CsfB 介导的对 σ 和 σ 的抑制至关重要,我们已经在体外对这些相互作用进行了表征。这项工作代表了我们对 CsfB 如何介导抑制两个替代σ因子以驱动细菌中发育基因表达的理解的一个进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6253/5890618/dbc5460d2e94/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6253/5890618/e3d78a22e440/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6253/5890618/adcc4fbd62c9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6253/5890618/ccbbf005ad9f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6253/5890618/769ee3bdf472/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6253/5890618/dbc5460d2e94/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6253/5890618/e3d78a22e440/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6253/5890618/adcc4fbd62c9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6253/5890618/ccbbf005ad9f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6253/5890618/769ee3bdf472/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6253/5890618/dbc5460d2e94/gr4.jpg

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